The proposed research is aimed at elucidation of relationships which may exist between variations in plasma membrane calcium transport and the expression of certain human diseases; inherited or acquired. To investigate plasma membrane transport of calcium, the red blood cell will be used. It is intended that the red blood cell serve as a model both of itself and of other cells in the body. Major emphasis will be on clarification of the regulation of calcium transport in normal human cells and possible variation(s) in such regulation in certain disease states. Disease states to be examined include sickle cell anemia, cystic fibrosis, and muscular dystrophy. The calcium pump is based on a membrane-bound (Ca 2 ion plus MG 2 ion)-ATPase. A cytoplasmic protein activator which is present in red blood cells increases the activity of the calcium pump ATPase. The hypothesis to be tested is that the cytoplasmic activator normally acts as a "switch" which turns on the plasma membrane calcium pump. Variations in quality and quantity of cytoplasmic activator protein, and the (Ca 2 ion plus Mg 2 ion)-ATPase and their interactions will be examined in normal red blood cells and red blood cells from patients. Likewise possible variations in calcium transport will be determined in red blood cells from patients. It is anticipated that results of the proposed research will provide further information on the plasma membrane calcium transport system in normal cells and variations which exist in certain diseases. ATPase activities will be determined on membranes isolated from red blood cells. Proteins will be isolated by standard techniques. Calcium transport will be determined in red blood cell and resealed red blood cell ghosts.